Supporting data for “Dysregulation of Methionine Metabolism of Hepatocytes Induced Epithelial-mesenchymal Transition of Hepatocytes and Abnormal Growth of Cholangiocytes in Biliary Atresia”

This research related to the hepatocytes and cholangiocyte organoids derived from iPSCs. These iPSC cell lines were derived from peripheral blood of patient with MAT1A mutation(BA638C) and a healthy control(HKUPS001). The specific MAT1A mutation was corrected to generate an iPSC cell line share the same genetic background with BA638C. Cholangiocyte organoids were also generated from the liver tissue of biliary atresia and non-biliary atresia patients.
This specific MAT1A mutation worked as a entry point to study the methionine metabolic dysfunction of hepatocytes and its relation to the biliary atresia pathogenesis. The data included in this item are the relevant sequencing results of hepatocytes and cholangiocyte organoids derived from the iPSC cell lines descrived above.
The results of this study indicates that (i) the MAT1A mutation induced EMT-like behavior of hepatocytes, potentially promoting liver fibrosis in disease progression; (ii) patients’ hepatocytes induced abnormal cholangiocyte development, which suggests that hepatocyte metabolic dysfunction can lead to cholangiocyte/bile duct injury in the initiation of BA.

本研究围绕诱导多能干细胞（induced pluripotent stem cell, iPSC）来源的肝细胞与胆管类器官展开。本研究的iPSC细胞系分别构建自携带MAT1A基因突变（BA638C）的患者外周血，以及健康对照个体（HKUPS001）；通过对该特异性MAT1A基因突变进行校正，可获得与BA638C株遗传背景一致的iPSC细胞系。此外，本研究还从胆道闭锁（biliary atresia）患者与非胆道闭锁患者的肝组织中分离得到胆管类器官。

该特异性MAT1A基因突变可作为探究肝细胞甲硫氨酸代谢紊乱及其与胆道闭锁发病机制关联的切入点。本数据集收录了上述iPSC细胞系来源的肝细胞与胆管类器官的相关测序结果。

本研究结果显示：① MAT1A基因突变可诱导肝细胞产生上皮间质转化（epithelial-mesenchymal transition, EMT）样表型，或在疾病进展中促进肝纤维化发生；② 患者来源的肝细胞可引发胆管细胞发育异常，提示在胆道闭锁（biliary atresia, BA）的起始阶段，肝细胞代谢紊乱可导致胆管细胞/胆管损伤。